Deposition of TAR DNA-binding 43 protein (TDP-43), especially phosphorylated TDP-43 (pTDP-43), into cytoplasmic and intranuclear inclusions is the pathological hallmark of frontotemporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS), as well as a common comorbid pathology in other neurodegenerative diseases, such as Alzheimer’s disease (AD)1–3. The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.